REVIEW

CURRENT
OPINION Laryngeal amyloidosis
Hannah Burns a and Nicholas Phillips b

Purpose of review
Laryngeal amyloidosis is a rare hematological disorder of plasma cells. The cause is still considered
idiopathic. The otolaryngology literature predominantly comprises case reports and short series. The
present review summarizes the amyloid literature more generally in order to assist the otolaryngologist
managing this disorder.
Recent findings
Distinguishing localized amyloidosis from systemic disease continues to be challenging. Both radiological
and hematological investigations may assist. Surgery continues to be the predominant modality for
treatment, but radiation and potentially medical approaches are on the horizon.
Summary
When localized, this benign laryngeal disease carries an excellent prognosis. Clinicians should however
be aware of systemic presentations and ensure patients receive long-term follow-up.
Keywords
laryngeal amyloidosis, localized amyloidosis, otolaryngology, plasma cells

INTRODUCTION AL is the most common form of amyloidosis

&&

Amyloidosis is characterized by the extracellular described [3 ]. In both systemic and localized

deposition of nonsoluble fibrillar proteins (amyloid)
within organs. Fibrils are a polymeric structure
arranged in hydrogen-bonded b pleated sheets
approximately 10 nm in diameter [1]. Other
components within the fibrils include serum P-com-
forms, a plasmacytic differentiated B-cell lympho-
proliferation secretes the light chain proteins, either
k, l, or both. The systemic form represents a plasma
cell dyscrasia, this may be mild increase in plasma
cells in the bone marrow, an overt plasma cell
&

ponent (SAP), which prevents degradation by pro- myeloma or a lymphoplasmacytic lymphoma [4 ].

teinases and heparin sulfate proteoglycan (HSPG), The localized form is less well understood but some
which provides an acidic substrate. Thirty-six dis- authors have identified similar localized lympho-
&

tinct human proteins can, in the correct environ-
ment, form pathological amyloid depositions [2 ].
&
The current classification system designates the
amyloid protein the letter A and the suffix reflects
the precursor protein name. Thus, amyloidosis light
chain (AL) describes immunoglobulin light chain,
AH, heavy chain, AA, apo serum amyloid A (an acute
phase reactant found in inflammatory conditions).
The older terminology of primary, describing AL,
and secondary describing AA is no longer used.
Amyloidosis may be localized or systemic, acquired
or inherited. AL and AH can occur as both systemic
and localized disease, whereas 14 other amyloids are
predominately systemic and the other 20 localized.
Systemic forms of amyloidosis produce the protein
in a central position, for example bone marrow or
liver and deposits the amyloid via the bloodstream
throughout the body. The localized form secretes
the abnormal material locally which does not tend
to spread outside that tissue.
proliferations [4 ]. Other theories suggest overex-
pression as a response to antigenic assault or a
failure in clearance of normal light chain produc-
tion. Mucosa-associated lymphoid tissue (MALT)
lymphoma has been associated with pulmonary
amyloidosis [5] and a more indolent MALT dyscrasia
may explain the site of localized deposits in other
aerodigestive and gastrointestinal sites. Laryngeal-
associated lymphoid tissue (LALT) has been
a
Department of Paediatric Otolaryngology, Queensland Children’s Hos-
pital, Brisbane, Queensland, Australia and bDepartment of Otolaryngol-
ogy, Toowoomba Base Hospital Queensland, Queensland, Australia
Correspondence to Hannah Burns, MBBS, BSc, FRACS, Senior Lec-
turer University Queensland, Department of Paediatric Otolaryngology,
Queensland Children’s Hospital, 501 Stanley St, South Brisbane, Qld
4101, Australia. Tel: +61 7 38615433; fax: +61 7 38615233;
e-mail: Hannah.burns@health.qld.gov.au
Curr Opin Otolaryngol Head Neck Surg 2019, 27:467–474
DOI:10.1097/MOO.0000000000000579

1068-9508 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-otolaryngology.com

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Laryngology and bronchoesophagology
KEY POINTS
 Amyloidosis is rarely recognized on initial presentation
and diagnosis is with histology confirmation showing
Congo red birefringence. Immunohistochemistry and
fibril typing are gold standard.
 A thorough history must be taken looking for
unrecognized systemic amyloidosis. Involvement of a
hematologist is recommended.
 I123 SAP, serum, and urine electrophoresis may assist
in excluding systemic disease but are very rarely
positive in patients with laryngeal amyloidosis. MRI is
recommended to assist with surgical planning and
prognosis.
 True localized laryngeal amyloidosis carries an
excellent prognosis but requires long-term follow-up.
 Antifibril biologics and radiation therapy may carry
future promise.
described anatomically throughout the larynx and
in highest concentrations in the supraglottis [6].
This may account for the predilection of amyloid
within the supraglottis. LALT and its counterpart,
bronchial-associated lymphoid tissue (BALT), are
found significantly more frequently in children,
suggesting that it is especially important during
times of increased antigenic exposure as is found
during childhood. This may support the theory of
increased antigenic exposure contributing to the
development of amyloidosis because of increased
stimulation of plasma cells [7].
Systemic amyloidosis
Systemic AL carries a poor prognosis. In the early-
phase symptoms are poorly differentiated, which
may cause delays in diagnosis. Fatigue, neuropathy,
and heart failure may not be initially recognized as
amyloidosis. Overtime deposits in kidney, liver, and
heart lead to inevitable organ damage, eventually
organ failure and death. Although rare, laryngeal
deposits have been described in systemic disease
[8,9]. Once diagnosed this hematological disorder
is traditionally treated with antiplasma-cell chemo-
therapy, dexamethasone, and, if the patient can
tolerate it, stem cell transplant. These treatments
however do little to the already deposited amyloid
proteins, thus monoclonal antibody-based therapy
&
directed against the amyloid fibrils themselves [10 ]
or against SAP and HSPG particles are in early trials
[11].
It is worth the otolaryngologist remembering
that tongue infiltration is a common site of
468 www.co-otolaryngology.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
deposition in systemic amyloidosis, with one third
of systemic AL patients developing this deposition.
Minor salivary glands may also demonstrate infil-
tration and are a possible source of tissue for diag-
nosis for systemic disease, with a 90% sensitivity of
systemic AL [3 ].
&&
Localized amyloidosis
Localized amyloidosis most commonly involves the
larynx, tracheobronchopulmonary tree, bowel,
&&
bladder, eyelids, and skin [3 ]. Localized amyloid-
osis is distinct from plasmacytoma in which the
cellular elements dominate over the extracellular
depositions. Extramedullary plasmacytomas are
rare, representing 3% of all plasma cell neoplasms
&
and less than 1% head and neck tumors [12 ,13].
Plasmacytomas although fairly indolent have a
transformation rate of 11–30% to multiple mye-
&
loma [12 ]. Although they are considered highly
radiosensitive, there are evidence supporting
surgical management for laryngeal extramedullary
&
plasmacytoma with favorable outcomes [12 ]. This
likely reflects improved microsurgical techniques in
centers with laryngeal cancer experience.
The larynx is the most common site of localized
amyloid deposition in the head and neck, however
only represents 1% of benign laryngeal tumors
&
[14,15 ]. It is predominately caused by AL protein
although cases involving other forms are described,
for example ApoA1 [16]. It is widely held that the
vast majority of cases represent a localized form and
are not associated with systemic disease. However,
rare cases of progression are reported, thus clinicians
need to be suspicious when encountering what
appears to be localized depositions [9].
Because of the rare nature of laryngeal amyloid,
the majority of the literature consists of single case
reports and small series of less than 22 cases
& & & & & & &
[14,15 ,17 ,18 ,19 ,20 ,21–33,34 ,35 ,36,37,38,39].
The largest cohorts have been described by the
National Amyloid Centre in the United Kingdom
[16], who described 92 patients with laryngeal or
tonsillar localized amyloidosis over a 31-year period
&&
and the Mayo amyloid clinic [40 ] with 57 patients
over a 46-year period.
&&
Males and females are equally affected [40 ] and
the average presentation occurs in the 5th decade
& &&
[16,35 ,40 ]. This is slightly younger than the
&&
systemic AL presentation [3 ]. A small number of
&
children have been described [18 ,32,41], with the
youngest reported at age 8. Although some papers
describe a predominantly Caucasian population
&
[35 ], many case cases have been reported in the
& &
Asian and North African literature [17 ,31,34 ]. Both
&&
Kourelis [40 ] and Mahmood [16] have found an
Volume 27  Number 6  December 2019

association with autoimmune conditions in 7–11%
of patients with localized AL.
Presentation
The most common presentation of laryngeal amy-
loidosis is dysphonia with stridor and dyspnea
&
occurring less frequently [15 ,28]. Rarely these
patients present with airway obstruction, however
tracheotomy has been described [36]. Coyle et al.
&
[18 ] report on a child with sleep disordered breath-
ing found to have supraglottic amyloidosis. Dyspha-
gia is rarely reported but may reflect involvement of
&
the pharynx or even esophagus [15 ]. Symptoms are
fairly indolent, and patients have likely had depo-
sitions for many months before discovered. It may
also present as an incidental finding during upper
&
gastrointestinal endoscopy [15 ,28].
Rarely is amyloid the recognized diagnosis at
initial fiberoptic examination. The deposits are usu-
ally submucosal and appear slightly yellow, they
may appear polypoid and red in color as the disease
progresses. Localization is most commonly to the
vestibular folds (false cords) or ventricle, followed by
the vocal folds (true cords), aryepiglottic folds, and
&
subglottis in order of decreasing frequency [32,35 ].
Transglottic involvement is common and deposits
may be unilateral or bilateral.
The initial appearance tends to lead to micro-
laryngoscopy and biopsy. The biopsied tissue dem-
onstrates characteristic apple green birefringence
with Congo red stain (Fig. 1). Although the vast
majority of laryngeal disease involves the light
chain protein, immunohistochemistry is recom-
mended to confirm this. The new gold standard
of fibril typing is mass spectrometric analysis [11].
It is thus possible to determine whether the fibril is
light chain and if so k or l in origin. This is helpful
when patients are found to have serum light chain
abnormalities on electrophoresis as if the fibril types
are identical this may increase suspicion of systemic
disease.
Non-AL laryngeal disease requires specific
involvement with a hematologist and may represent
inherited forms of amyloidosis, for example ATTHR
&
[15 ] or ApoA1 [42]. No cases of AA amyloidosis
involving the larynx have been reported in the
literature. Gene sequencing must be performed in
cases of hereditary amyloidosis and online databases
of recognized mutations exist [43]. Histology will
also identify a plasma cell population, which should
be polyclonal.
It is important during initial microlaryngoscopy
to examine the upper airway and tracheobronchial
tree. Cases of laryngeal disease with coexisting
upper airway, for example Walder’s ring have been
1068-9508 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Laryngeal amyloidosis Burns and Phillips
described [14]. Tracheobronchial amyloidosis may
&
exist with laryngeal disease [17 ,36]. Pulmonary AL
amyloidosis rarely involves the larynx.
Investigations
The authors recommend all patients with laryngeal
amyloidosis have imaging of their airway to assess
extent of disease and potentially identify other
localized deposits. MRI is the ideal modality dem-
onstrating characteristic intermediate signal on T1
comparable with skeletal muscle, enhancement
with contrast and a low T2 signal, reflecting the
low water content [44] (Fig. 2). Imaging should
include the tracheobronchial tree to exclude more
diffuse disease. This information assists the surgeon
in planning treatment, provides prognosis on the
ability to completely remove the deposit, and aids
long-term follow-up. CT is less useful and without
biopsy results, may be confused with a malignant
&
process [45 ].
I123 SAP scintigraphy is a nuclear scanning tech-
nique, with 90% sensitivity for systemic amyloid
[46]. It is not widely available and predominantly
used in managing systemic disease in major centers.
The UK National Amyloid Centre has used this
technique since 1988 for all their amyloidosis
patients and in their series of 606 patients with
localized disease no patient had visceral organ
uptake at diagnosis and as such they excluded sys-
temic disease [16]. Similarly, PET scans have been
investigated. Glaudemans et al. [47] found 18F-FDG
PET/CT positive in 10 of 11 patients with localized
amyloidosis but 0 of 10 amyloid proven sites in
patients with systemic disease. Suggesting a role
in determining localized from systemic disease.
None of these patients had laryngeal involvement.
At present there is controversy in the literature
regarding the appropriate exclusion of systemic dis-
ease in the setting of laryngeal amyloidosis. The
Mayo clinic requires a negative result on serum
and urine immunofixation to be considered local-
&&
ized [40 ]. In comparison, the UK National Amyloid
Centre includes patients with abnormal serum light
chain ratios, providing there is no visceral organ
involvement on 123I SAP scintigraphy [16]. These
differences in classification between 2 large amyloid
centers highlight the difficulty faced by physicians
attempting to delineate between localized and sys-
temic amyloidosis. In one recent study, a Mayo
physician states that patients with localized AL
amyloidosis of the larynx do not need any inves-
tigations because of the very rare nature of this
&
disease being associated with systemic disease [48 ].
In the absence of previously diagnosed systemic
disease, in a patient without symptoms of systemic
www.co-otolaryngology.com 469
Laryngology and bronchoesophagology

FIGURE 1. Low power (40 magnification) Congo red staining: apple green birefringence is demonstrated on polarized light.

disease and no family history of amyloidosis, it may
be reasonable that, under consultation with your
local hematology team, patients may not need any
further investigations. If the diagnosis is uncertain,
urinary screen for proteinuria and bloods to
determine normal liver and renal function is non-
invasive and cost effective, whereas serum and urine
electrophoresis for immunoglobulins can also be
considered. Patients with abnormalities on these
tests, under hematological guidance, require bone

470 www.co-otolaryngology.com Volume 27  Number 6  December 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

 Laryngeal amyloidosis Burns and Phillips

FIGURE 2. MR axial (a) and coronal (c) demonstrate intermediate signal comparable with skeletal muscle on T1 (images a
and c), whereas axial (b) and coronal (d) demonstrate enhancement post-contrast highlighting amyloidosis occupying the
supraglottis bilaterally involving the false cords.

marrow biopsy. Abdominal fat biopsy carries a 60–
&&
80% sensitivity for systemic AL amyloidosis [3 ].
Cardiology review for cardiac infiltration is recom-
mended, for patients with systemic disease [11].
The literature describes laryngeal AL patients
with abnormalities on their hematological work
up but without other findings of systemic disease
[16,49]. Whether these cases truly represent local-
ized AL is unclear. The risk of developing systemic
amyloidosis is exceptionally low. Of the 606
patients in the UK study with localized disease only
seven developed systemic AL amyloidosis. None of
these patients had laryngeal disease. Six of these
patients also had abnormal circulating immunoglo-
bulins at presentation, thus highlighting a particu-
lar need to monitor patients with hematological
abnormalities [16]. Similarly, the Mayo clinic
reported no systemic development in any patient
with localized amyloidosis in their cohort of 413
&&
patents [40 ]. Abnormalities in serum light chains
at presentation however excluded a diagnosis of
localized disease in the first instance, thus poten-
tially selecting out this high-risk group at an earlier
&
timeframe. Rudy et al. [35 ] reported one case in a

1068-9508 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-otolaryngology.com 471

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Laryngology and bronchoesophagology
FIGURE 3. Appearance on microlaryngoscopy of amyloidosis deposit occupying supraglottis and glottis with obstruction of
laryngeal inlet. Pretreatment (a) and posttreatment (b) after coblation wand excision.
series of 22 patients with laryngeal amyloidosis who
developed systemic AL 10 years after the initial
airway diagnosis. Three other patients developed
amyloid at a second site.
Patients with previously diagnosed systemic dis-
ease can develop deposits in their larynx and airway
[50]. These patients are treated as per systemic regime
but may require localized treatment as well. It
appears, in most cases, that systemic treatment is
unlikely to manage the laryngeal component despite
good systemic control. Thus, once deposited the
fibrils do not undergo regression with the current
medical management. Clinical trials of monoclonal
antibodies directed towards the light chain proteins
&
or SAP are in their infancy [10 ]. Curcumin (the active
ingredient in turmeric) use has been reported in one
case of systemic disease with laryngeal involvement
to halt progression [50], however evidence is limited
with only one other study reporting no change for
localized AL [32]. A number of other novel anti-fibril
treatments are under investigation for systemic amy-
loidosis, including doxycycline and green tea [51].
Likewise, no medical treatment for localized laryn-
geal disease has been described. The development of
monoclonal antibodies for systemic disease may
carry implications for localized disease but as yet
no authors have described this possibility.
Treatment
The mainstay of treatment remains surgical
removal or debulking. Given the organ involved
it is often not possible to remove all the
deposit. Predominantly, these patients are
managed endoscopically or microscopically using
microlaryngoscopy techniques. Cold steel [38], CO2
472 www.co-otolaryngology.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
&
laser [15 ,36], KTP laser [31], Nd:YAG [36] micro-
&
derider [18 ], and coblator [32] have all been
described. It would not appear that any one modal-
ity holds superiority over another. The goal of sur-
gery should be to remove as much of the deposition
as possible while maintaining laryngeal function
(Fig. 3). Some authors advocate a staged approach to
resection [52], and observation may be appropriate
for small volume disease. Cases of open resection via
laryngofissure describe good airway results [22].
Subglottic disease can be debulked with similar
endoscopic techniques. Dilation with balloons
has also been described for patients with subglottic
extension [32].
Despite dysphonia being the most common
presenting symptom, few papers present objective
voice measurement. Hazenberg et al. [49] presented
preoperative voice data in eight patients with laryn-
geal disease, although reporting positive changes
post operatively none of these results where statisti-
cally significant. Endoscopic approaches likely give
better voice outcomes with open resections describ-
ing the development of webbing and vocal cord
fixation [22].
Patients with airway symptoms are more likely
to have glottic and/or subglottic involvement. How-
ever, supraglottic disease if bulky enough may cause
airway obstruction, including sleep disordered
&
breathing [18 ]. Case reports of death because of
airway obstruction [41] and patients needing trache-
otomy for airway management [39] or to facilitate
treatment [36] are described. Because of its benign
nature more aggressive management is rarely indi-
cated however laryngectomy has been reported [36].
Tracheobronchial disease can be exceptionally
challenging and may require recurrent debridement
Volume 27  Number 6  December 2019

to maintain airway patency, with ‘‘cure’’ highly
unlikely. The use of stents in severe disease has been
reported [36,37]. Piazza describes seven patients
with tracheal involvement who developed tracheo-
bronchopatia osteochondroplastica [36]. This is a
rare condition in which the trachea develops carti-
laginous or osseous nodules. The narrowing caused
by this complication can lead to dyspnea and airway
compromise. The relationship between these two
conditions is unknown.
Follow up and prognosis
Follow up is essential in all cases and recurrence is
common. This reflects the infiltrative nature of the
disease and the inability to remove all amyloid
without severe consequences to the voice, swallow
or airway. Hazenberg et al. [49] reported on the long-
term follow up with two thirds of patients required
a second operation and the half of these again
required a further debulking. Interestingly, the
majority of patients burnt out locally after approxi-
mately 7 years.
Although cases of recurrence are typically
treated with further resection, there are several
reports of localized disease treated with low-dose
(20–45Gy) radiation therapy [53,54]. It is hypothe-
sized that radiation therapy eliminates the amyloi-
dogenic local plasma cells and arrests disease
progression [53]. Given the fairly indolent nature
of localized disease, a randomized controlled trial
would assist determining whether this treatment
modality carries any merit. The ideal dose is likewise
undetermined.
Long-term survival is significantly higher for
localized disease with 5-year survival rates of 91
versus 37% for systemic disease [16]. Mortality rates
for laryngeal disease is very low, however death
secondary to airway obstruction and massive upper
airway hemorrhage have been reported [37,39].
More diffuse disease involving the laryngotracheo-
bronachial sites are at higher risk with 4 of 32
patients with distal bronchial disease dying in one
series [36].
CONCLUSION
Thirty-six distinct proteins can form amyloid with
light chain immunoglobulin protein the most com-
mon. AL amyloidosis is a rare hematological disor-
der of plasma cells that can present in a systemic or
localized pattern. The localized form carries a better
prognosis and its cause is still considered idiopathic.
Within the head and neck the larynx is the most
common site of amyloid depositions with the supra-
glottis being the most common site. However, all
1068-9508 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Laryngeal amyloidosis Burns and Phillips
sites of the larynx and throughout the entire aero-
digestive tract are described. This may represent sites
of MALT/LALT/BALT. It is almost never associated
with systemic AL, however, as systemic AL can also
form deposits in the larynx a high level of suspicion
is required, and involvement of a hematologist is
recommended. The need for investigations is still
controversial. MRI gives ideal imaging to assist in
management. In symptomatic patient’s endoscopic
management is now the preferred modality. Com-
plete removal may be impractical, and many
patients live with small volume disease. The role
of XRT is undetermined. Long-term follow up is
recommended. New biologics targeting amyloid
fibrils may carry future treatment options.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Cohen AS, Calkins E. Electron microscopic observations on a fibrous
component in amyloid of diverse origins. Nature 1959; 183:1831202a0.
2. Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018:
recommendations by the International Society of Amyloidosis (ISA) nomen-
&
clature committee. Amyloid 2018; 25:215–219.
Updated biyearly by the ISA, this document provides a classification framework for
all forms of amyloidosis
3. Vaxman I, Gertz M. Recent advances in the diagnosis, risk stratification, and
&& management of systemic light-chain amyloidosis. Acta Haematologica 2019;
141:93–106.
Review from the Mayo clinic amyloid center discussing systemic AL from diag-
nosis, investigations and management. Short discussion on localized AL
4. Stuhlmann-Laeisz C, Schönland SO, Hegenbart U, et al. AL amyloidosis with
& a localized B cell neoplasia. Virchows Archiv 2019; 474:353–363.
Proposes a classification systemic for localized AL which describes a range of B-
cell lymphoproliferative disorders ranging from true plasmacytoma, localized B-cell
lymphoma through to a local clonal infiltration
5. Core JM, Alsaad AA, Jiang L, Patel NM. Nodular pulmonary amyloidosis: a
complex disease with malignancy association. BMJ Case Rep 2017; pii: bcr-
2017-220428.
6. Kracke A, Hiller A, Tschernig T, et al. Larynx-associated lymphoid tissue
(LALT) in young children. Anatomical Rec 1997; 248:413–420.
7. Hiller AS, Tschernig T, Kleemann WJ, Pabst R. Bronchus-associated lym-
phoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) are found
at different frequencies in children, adolescents and adults. Scand J Immunol
1998; 47:159–162.
8. Bartels H, Dikkers FG, Lokhorst HM, et al. Laryngeal amyloidosis: localized
versus systemic disease and update on diagnosis and therapy. Ann Otology
Rhinol Laryngol 2004; 113:741–748.
9. Ginat DT, Schulte J, Portugal L, Cipriani NA. Laryngotracheal involvement in
systemic light chain amyloidosis. Head Neck Pathol 2017; 12:127–130.
10. Bhutani D, Leng S, Lentzsch S. Fibril directed therapies in systemic light chain
& AL amyloidosis. Clin Lymphoma Myeloma Leuk 2019; 19:555–559.
A review of the emerging fibril directed therapies for systemic AL.
11. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet
2016; 387:2641–2654.
www.co-otolaryngology.com 473
Laryngology and bronchoesophagology
12. Ge S, Zhu G, Yi Y. Extramedullary plasmacytoma of the larynx: literature
& review and report of a case who subsequently developed acute myeloid
leukemia. Oncol Lett 2018; 16:2995–3004.
A comprehensive literature review of laryngeal plasmacytoma, discussing treat-
ment modalities and prognosis
13. Loyo M, Baras A, Akst LM. Plasmacytoma of the larynx. Am J Otolaryng 2013;
34:172–175.
14. Passerotti G, Caniello M, Hachiya A, et al. Multiple-sited amyloidosis in the
upper aerodigestive tract: case report and literature review. Braz J Otorhinolar
2008; 74:462–466.
15. Send T, Spiegel JL, Schade G, et al. Amyloidosis of the upper aerodigestive
& tract: management of a rare disease and review of the literature. Dysphagia
2019; 34:179–191.
A small series of various aerodigestive presentations of amyloidosis. Includes a
case of hereditary amyloidosis with laryngeal disease. Proposes an algorithm for
head and neck amyloidosis workup.
16. Mahmood S, Bridoux F, Venner CP, et al. Natural history and outcomes in
localised immunoglobulin light-chain amyloidosis: a long-term observational
study. Lancet Haematol 2015; 2:e241–e250.
17. Deepak D, Kishore M, Bhardwaj M, Chugh P. Localized laryngotracheobron-
& chial amyloidosis: management issues. Lung India Official Organ Indian Chest
Soc 2019; 36:173–175.
A case describing an initial diagnosis of laryngeal AL in whom distal tracheobron-
chial disease was later diagnosed. Highlighting the importance of bronchoscopy
and imaging in patients with laryngeal presentations.
18. Coyle P, Tan N, Jonas N. Sleep disordered breathing and dysphonia in a
& pediatric patient – laryngeal amyloidosis as an unusual diagnosis. Int J Pediatr
Otorhi 2019; 122:44–46.
An unusual presentation of amyloidosis in a child, with supraglottic disease treated
successfully using a microdebrider
19. Zainol S, Azman M, Muthusamy S. Isolated laryngeal amyloidosis: a case
& report. Egypt J Otolaryngol 2018; 34:359–362.
A typical case study of laryngeal AL presenting with dysphonia and successfully
treated with CO2 laser
20. Tawab HM, Sulaiman IA. Localized subglottic laryngeal amyloidosis: a case
& report. Egypt J Otolaryngol 2018; 34:337–340.
Further case study from the Egyptian literature.
21. Agius M, Grima T, Cvorovic M, et al. A case report on localised laryngeal
amyloidosis. Int J Otorhinolaryngol Head Neck Surg 2017; 3:732–734.
22. Szőcs M, M€ uhlfay G, Mocan S, et al. Localized laryngeal amyloidosis - a case
report. Romanian J Morphol Embryol 2015; 56:597–600.
23. Kise Y, Katoh A, Takenaga F, et al. A Case of Laryngeal Amyloidosis. Pract
Oto-rhino-laryngologica Suppl 2014; 138:78–79.
24. Bouaity B, Darouassi Y, Touati M, et al. Laryngeal amyloidosis, report of a new
case and review of the literature. Egypt J Ear Nose Throat Allied Sci 2014;
15:263–265.
25. Celenk F, Durucu C, Baysal E, et al. Management of upper aerodigestive tract
amyloidosis. Ann Otology Rhinol Laryngol 2013; 122:535–540.
26. Lee E, Yang Y, Kim J, Hong K. A ‘Boxer Glove’ contoured laryngeal amyloi-
dosis. Clin Exp Otorhinolar 2012; 5:240–242.
27. Chow V, Gardner K, Howlett D. Primary localized laryngeal amyloidosis
presenting with dysphonia: a case report. J Surg Case Rep 2012;
2012:rjs005.
28. Penner CR, Műller S. Head and neck amyloidosis: a clinicopathologic study of
15 cases. Oral Oncol 2006; 42:421–429.
29. Wang Q, Chen H, Wang S. Laryngo-tracheobronchial amyloidosis: a case
report and review of literature. Int J Clin Exp Patho 2014; 7:7088–7093.
30. Alaani A, Warfield A, Pracy J. Management of laryngeal amyloidosis. J
Laryngology Otol 2004; 118:279–283.
31. Deviprasad D, Pujary K, Balakrishnan R, Nayak D. KTP laser in laryngeal
amyloidosis: five cases with review of literature. Indian J Otolaryngol 2013;
65:36–41.
32. Phillips N, Matthews E, Altmann C, et al. Laryngeal amyloidosis: diagnosis,
pathophysiology and management. J Laryngol Amp Otol 2017; 131:
S41–S47.
33. Pribitkin E, Friedman O, O’Hara B, et al. Amyloidosis of the upper aero-
digestive tract. Laryngoscope 2003; 113:2095–2101.
474 www.co-otolaryngology.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
34. Gosavi SR. Primary laryngeal amyloidosis: a discussion of 10 cases with a
& review of the literature. Int J Phonosurg Laryngol 2018; 8:52–60.
A series of 10 cases from an Indian department, describing a range of presenta-
tions including one patient with a plasmacytoma
35. Rudy SF, Jeffery CC, Damrose EJ. Clinical characteristics of laryngeal versus
& nonlaryngeal amyloidosis. Laryngoscope 2018; 128:670–674.
A retrospective review of 22 patients with laryngeal amyloidosis from the Stanford
Amyloid Centre. One of whom had a prior systemic AL diagnosis and 3 who
developed seemingly secondary localized sites. The laryngeal patients were less
likely to have a hematological disorder compared to control patients with non-
laryngeal deposits.
36. Piazza C, Cavaliere S, Foccoli P, et al. Endoscopic management of laryngo-
tracheobronchial amyloidosis: a series of 32 patients. Eur Arch Oto-rhino-l
2003; 260:349–354.
37. Paccalin M, Hachulla E, Cazalet C, et al. Localized amyloidosis: a survey of 35
French cases. Amyloid 2009; 12:239–245.
38. Wierzbicka M, Budzyński D, Piwowarczyk K, et al. How to deal with laryngeal
amyloidosis? Experience based on 16 cases. Amyloid 2012; 19:177–181.
39. Mäkitie AA, Vala U, Kronlund H, et al. Laryngeal amyloidosis as a cause of
death. Amyloid 2013; 20:. doi:10.3109/13506129.2013.763785.
40. Kourelis TV, Kyle RA, Dingli D, et al. Presentation and outcomes of localized
&& immunoglobulin light chain amyloidosis the mayo clinic experience. Mayo Clin
Proc 2017; 92:908–917.
Although outside the review period, this Mayo clinic review describes one of the
largest series of laryngeal amyloidosis. It describes the Mayo clinic protocol for
excluding systemic disease, that is negative results on urine and serum immuno-
histochemistry
41. Mitrani M, Biller HF. Laryngeal amyloidosis. Laryngoscope 1985; 95:
1346–1347.
42. Hazenberg AJ, Dikkers FG, Hawkins PN, et al. Laryngeal presentation of
systemic apolipoprotein A-I–derived amyloidosis. Laryngoscope 2009;
119:608–615.
43. Rowczenio DM, Noor I, Gillmore JD, et al. Online registry for mutations in
hereditary amyloidosis including nomenclature recommendations. Hum Mutat
2014; 35.
44. Parmar H, Rath T, Castillo M, Gandhi D. Imaging of focal amyloid depositions
in the head, neck, and spine: amyloidoma. Am J Neuroradiol 2010;
31:1165–1170.
45. Muneeb A, Gupta S. Isolated laryngeal amyloidosis mimicking laryngeal
& cancer. Cureus 2018; 10:e3106.
Describes the difficulty of diagnosis without histological findings.
46. Sachchithanantham S, Wechalekar AD. Imaging in systemic amyloidosis. Brit
Med Bull 2013; 107:41–56.
47. Glaudemans AW, Slart RH, Noordzij W, et al. Utility of 18F-FDG PET(/CT) in
patients with systemic and localized amyloidosis. Eur J Nucl Med Mol I 2013;
40:1095–1101.
48. Gertz MA. Immunoglobulin light chain amyloidosis: 2018 Update on diag-
& nosis, prognosis, and treatment. Am J Hematol 2018; 93:1169–1180.
Biyearly update from the Mayo Amyloid Clinic on managing AL, both systemic and
localized.
49. Hazenberg AJ, Hazenberg BP, Dikkers FG. Long-term follow-up after surgery
in localized laryngeal amyloidosis. Eur Arch Oto-rhino-l 2016; 273:
2613–2620.
50. Golombick T, Diamond TH, Manoharan A, Ramakrishna R. Stabilisation of
laryngeal AL amyloidosis with long term curcumin therapy. Case Rep Hematol
2015; 2015:1–4.
51. Muchtar E, Gertz MA. Clinical trials evaluating potential therapies for light
chain (AL) amyloidosis. Expert Opin Orphan Drugs 2017; 94:. doi:10.1080/
21678707.2017.1341834.
52. Walker PA, Courey MS, Ossoff RH. O: Staged endoscopic treatment of
laryngeal amyloidosis. Otolaryngology - Head Neck Surg 1996; 114:
801–805.
53. Truong M, Kachnic LA, Grillone GA, et al. Long-term results of conformal
radiotherapy for progressive airway amyloidosis. Int J Radiat Oncol Biol Phys
2012; 83:734–739.
54. Neuner GA, Badros AA, Meyer TK, et al. Complete resolution of laryngeal
amyloidosis with radiation treatment. Head Neck 2012; 34:748–752.
Volume 27  Number 6  December 2019